We propose to organize a meeting titled Critical Assessment of Genome Interpretation (CAGI) in December 2011. The meeting will be the culmination of a community experiment to objectively assess computational methods for predicting the phenotypic impacts of genomic variation. The CAGI experiment is timely and of wide relevance because of the burgeoning availability of individuals'genomes, and the desire to interpret them for research and clinical applications. Currently, the field lacks a consensus on the absolute and relative suitability of the panoply of different methods for prediction. This meeting will provide the first large-scale assessment of the state of the art of genome variation interpretation, and outcome of the meeting will be published to ensure wide dissemination of the results. In the CAGI experiment, modeled on the Critical Assessment of Structure Prediction (CASP), participants are provided genetic variants and will make predictions of resulting molecular, cellular, or organismal phenotype. Datasets are expected to include rare disease, common traits and diseases, germline and somatic cancer variation, with a focus on nsSNPs, splice-affecting SNPs, exomes, and copy number variation. Independent assessors will evaluate the predictions against experimentally characterized phenotypes. The CAGI Conference is held at the end of the experiment. The specific goals of the meeting are: (1) to assess the quality of current computational methods for interpreting genomic data, and highlight innovations &progress;(2) to guide future research efforts in computational genome interpretation and build a strong community for collaboration and interaction;and (3) to disseminate results both amongst key members of the variant-phenotype prediction community at the meeting and to broader audience via publication of results in peer-reviewed journals. This will be the first full-scale CAGI experiment. In fall 2010 we organized the preliminary CAGI experiment, which yielded 108 predictions on 6 datasets, from 17 groups in 8 countries. Forty people attended the December 2010 workshop and seven viewed the live feed of the meeting. The community was unanimous that this experiment is necessary and should be organized again on a larger scale. The organizers will strongly encourage the participation of women and minorities, and broad participation of trainees and senior scientists at the CAGI meeting. Funding is requested for awarding 19 trainee fellowships for students and postdoctoral researchers to cover approximately 2/3 of their meeting participation costs (travel, registration, and subsistence). In addition, we seek funding to subsidize half of meeting participation costs of independent assessors and organizers of the CAGI experiment. PUBLIC HEALTH RELEVANCE: Genomic variation is responsible for numerous rare diseases, propensity for many common traits and diseases, and is a key characteristic of cancer evolution. At present, our ability to characterize genetic differences far exceeds our capacity to interpret it either for basic research understanding or for clinical diagnosis. The Critical Assessment of Genome Interpretation will provide an evaluation of the current state-of- the-art and help promote progress to understand genomic variation.